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High Fetal Estrogen Levels Linked to Autism

By Labmedica International staff writers
Posted on 14 Aug 2019
The male-biased prevalence of autism, together with the finding that autistic girls have a higher mutational load than autistic boys, suggests that males have a higher likelihood of developing autism.

Although autism is strongly heritable and sex-associated genetic mechanisms could contribute to this implication of sexual differentiation in autism, prenatal hormone exposure and a brief surge in fetal testosterone are critical for sexual differentiation and masculinization in humans.

Image: The Xevo TQ-S micro Triple Quadrupole Mass Spectrometry (Photo courtesy of Waters).
Image: The Xevo TQ-S micro Triple Quadrupole Mass Spectrometry (Photo courtesy of Waters).

An international team of scientists led by those at the University of Cambridge (Cambridge, UK) testing the amniotic fluid samples from the same 98 individuals sampled from the Danish Biobank, which has collected amniotic samples from over 100,000 pregnancies. The team concentrated at investigating prenatal sex steroid hormones called estrogens. This is an important next step because some of the hormones previously studied are directly converted into estrogens.

The amniotic fluid samples were assayed for estradiol, estriol, estrone, and estrone sulphate, using liquid chromatography-tandem mass spectroscopy. The LC-MS/MS setup consisted of an Acquity Ultra Performance Liquid Chromatography machine with an Acquity sample manager and an Acquity sample organizer, followed by Xevo TQ-S triple quadrupole mass spectrometer equipped with an electron spray ionization probe.

The scientists reported that all four estrogens were significantly elevated, on average, in the 98 fetuses that later developed autism, compared to the 177 fetuses who did not. High levels of prenatal estrogens were even more predictive of likelihood of autism than were high levels of prenatal androgens, such as testosterone. Contrary to popular belief that associates estrogens with feminization, prenatal estrogens have effects on brain growth and also masculinize the brain in many mammals.

The authors concluded that they had demonstrated that prenatal estradiol, estriol and estrone are elevated in boys who went on to develop autism. High levels of prenatal estradiol contribute to a greater degree to autism likelihood than other prenatal sex steroids, including testosterone. Prenatal estrogenic excess is a characteristic of autism and may interact with genetic predisposition to affect neurodevelopment. The study was published on July 29, 2019, in the journal Molecular Psychiatry.

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University of Cambridge

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